Capturing and Manipulating Activated Neuronal Ensembles with CANE Delineates a Hypothalamic Social-Fear Circuit

Neuron. 2016 Nov 23;92(4):739-753. doi: 10.1016/j.neuron.2016.10.015. Epub 2016 Oct 27.


We developed a technology (capturing activated neuronal ensembles [CANE]) to label, manipulate, and transsynaptically trace neural circuits that are transiently activated in behavioral contexts with high efficiency and temporal precision. CANE consists of a knockin mouse and engineered viruses designed to specifically infect activated neurons. Using CANE, we selectively labeled neurons that were activated by either fearful or aggressive social encounters in a hypothalamic subnucleus previously known as a locus for aggression, and discovered that social-fear and aggression neurons are intermixed but largely distinct. Optogenetic stimulation of CANE-captured social-fear neurons (SFNs) is sufficient to evoke fear-like behaviors in normal social contexts, whereas silencing SFNs resulted in reduced social avoidance. CANE-based mapping of axonal projections and presynaptic inputs to SFNs further revealed a highly distributed and recurrent neural network. CANE is a broadly applicable technology for dissecting causality and connectivity of spatially intermingled but functionally distinct ensembles.

Keywords: CANE; Fos; VMHvl; activity dependent; aggression; functional neural circuit; hypothalamus; social fear.

Publication types

  • Video-Audio Media

MeSH terms

  • Aggression*
  • Animals
  • Axons / metabolism
  • Axons / physiology
  • Behavior, Animal / physiology*
  • Fear / physiology*
  • Gene Knock-In Techniques
  • Hypothalamus / cytology*
  • Hypothalamus / metabolism
  • Hypothalamus / physiology
  • Mice
  • Nerve Net / metabolism
  • Nerve Net / physiology*
  • Neurons / metabolism
  • Neurons / physiology*
  • Optogenetics
  • Proto-Oncogene Proteins c-fos / metabolism
  • Social Behavior*
  • Ventromedial Hypothalamic Nucleus / cytology
  • Ventromedial Hypothalamic Nucleus / metabolism
  • Ventromedial Hypothalamic Nucleus / physiology


  • Proto-Oncogene Proteins c-fos